Please use this identifier to cite or link to this item:
Title: Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex
Authors: Gao, C.
Dimitrov, T.
Yong, K.J.
Tatetsu, H.
Jeong, H.-W.
Luo, H.R.
Bradner, J.E.
Tenen, D.G. 
Chai, L.
Issue Date: 21-Feb-2013
Citation: Gao, C., Dimitrov, T., Yong, K.J., Tatetsu, H., Jeong, H.-W., Luo, H.R., Bradner, J.E., Tenen, D.G., Chai, L. (2013-02-21). Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex. Blood 121 (8) : 1413-1421. ScholarBank@NUS Repository.
Abstract: An exciting recent approach to targeting transcription factors in cancer is to block formation of oncogenic complexes. We investigated whether interfering with the interaction of the transcription factor SALL4, which is critical for leukemic cell survival, and its epigenetic partner complex represents a novel therapeutic approach. The mechanism of SALL4 in promoting leukemogenesis is at least in part mediated by its repression of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through its interaction with a histone deacetylase (HDAC) complex. In this study, we demonstrate that a peptide can compete with SALL4 in interacting with the HDAC complex and reverse its effect on PTEN repression. Treating SALL4-expressing malignant cells with this peptide leads to cell death that can be rescued by a PTEN inhibitor. The antileukemic effect of this peptide can be confirmed on primary human leukemia cells in culture and in vivo, and is identical to that of down-regulation of SALL4 in these cells using an RNAi approach. In summary, our results demonstrate a novel peptide that can block the specific interaction between SALL4 and its epigenetic HDAC complex in regulating its target gene, PTEN. Furthermore, targeting SALL4 with this approach could be an innovative approach in treating leukemia. © 2013 by The American Society of Hematology.
Source Title: Blood
ISSN: 00064971
DOI: 10.1182/blood-2012-04-424275
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Oct 20, 2021


checked on Oct 20, 2021

Page view(s)

checked on Oct 14, 2021

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.